. New therapies are urgently needed to treat AD patients, but we have no biomarker to determine when to start treatment and we lack approaches to predict the onset of disease and the outcome of therapeutics. The slow movement towards effective therapeutics brings us to a juncture at which longstanding approaches to drug discovery are no longer sufficient to identify successful therapeutics. New methods are needed if we are to improve the outcome of clinical trials or to develop more effective therapies. We have established a new platform for treating AD patients and new kind of biomarker to follow efficacy. The platform is XJB-5-131, a powerful electron scavenger which exerts its effects by targeting mitochondria (MT) directly and, among other effects, neutralizes oxygen damage and inflammation. The new biomarker is the spectral phenotype of the cell. Different from more conventional endpoints, we will used Fourier transform infrared light (FTIR) spectromicroscopy to follows changes in cell chemistry. The new biomarker method is powerful because cell chemistry changes in the disease state and in in response to drugs. FTIR is sensitive enough to detect both the disease state and drug effects. These findings arose from evaluating the effects of XJB-5-131 in HD animal models. In this proposal, we will apply the methods to AD animal models and in human AD fibroblasts. Animals with distinct mutational backgrounds will be tested for the timing and extent of their response using the FTIR biomarkers. AD fibroblasts with no known disease-causing mutation will be grouped according to the FTIR signature. We will test whether patients in the same FTIR class, i.e., the same chemistry, respond the same way to XJB-5-131. The goal is to develop an effective therapy and a new biomarker to evaluate when to start treatment and to predict the onset and outcome of treatment.
We will use spectral phenotyping to uniquely classify Alzheimer?s mice and patients as to origin and for cell type disturbances in tissue and complex environments. We will develop Spectral Phenotyping by Synchrotron Radiation Fourier-transform Infrared spectromicroscopy (SR-FTIR). Spectral phenotyping is a powerful and nondestructive technology, which provides label-free fingerprint-like spectra originating from the characteristic vibrational frequencies of various chemical bonds.
